We performed a systematic review and meta-analysis to investigate the effects of vitamin D (VitD) supplementation on children with allergic diseases. MEDLINE, Embase, Web of Science, the Cochrane library, and three Chinese databases were searched up to 15 August 2022. Randomized controlled trials (RCTs) comparing a VitD supplementation versus a placebo for children with allergic diseases were included. Thirty-two RCTs with 2347 participants were included. VitD supplementation did not reduce the risk of asthma exacerbations in children compared with placebo overall (risk ratio (RR) = 0.84, 95% confidence interval (CI): 0.65 to 1.08, p = 0.18), but reduced the risk of asthma exacerbation in children with baseline serum 25(OH)D of <10 ng/mL compared with placebo (RR = 0.48, 95% CI: 0.28 to 0.83, p = 0.009). VitD supplementation significantly reduced Scoring Atopic Dermatitis or the Eczema Area and Severity Index scores in children with atopic dermatitis compared with placebo (standard mean difference = −0.5, 95% CI: −0.87 to −0.12, p = 0.009). VitD supplementation also reduced the symptom-medication score in children with allergic rhinitis compared with placebo (mean (standard deviation): 43.7 (3.3) vs. 57.8 (4.4), p = 0.001). In conclusion, VitD supplementation did not reduce asthma exacerbation risk in children overall but may reduce asthma exacerbation risk in children with serum 25(OH)D concentration < 10 ng/mL. VitD supplementation reduces the severity of atopic dermatitis and symptoms of allergic rhinitis in children.

The cytokine storm, a life-threatening systemic inflammatory syndrome, is the primary driver of multiorgan failure in different clinical situations, including severe infections, autoimmune diseases, chimeric antigen receptor (CAR) T cell immunotherapy for cancer, and genetic syndromes. This review focuses primarily on cytokine storms triggered by severe infections such as viral pneumonia and bacterial sepsis, and explores the underlying mechanisms of cytokine storms and potential therapeutic interventions. Cytokine storms are characterized primarily by the excessive release of proinflammatory cytokines, which are triggered by pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and PANoptosis, all of which activate immune signaling cascades. Amplification mechanisms involve positive feedback loops and the failure of negative feedback mechanisms, leading to uncontrolled inflammation. Like a pyrrhic victory, the excessive activation of the immune system eliminated invading pathogens but caused catastrophic damage due to multiple organ dysfunction syndrome (MODS), turning the life-saving response into a life-threatening war. Therapeutic strategies, including cytokine antagonists, Janus kinase (JAK) inhibitors, caspase inhibitors, glucocorticoids, and blood purification therapies, aim to interrupt the self-amplifying cycle of inflammation that propagates organ injury, thereby reducing MODS and mortality. Challenges include optimizing the treatment timing and patient stratification. Future research should focus on combination therapies and personalized medicine based on the heterogeneity of infections and sepsis. Advances in multiomics and targeted therapies provide new hope for managing infections and sepsis.

Sepsis remains a leading global health challenge, with delayed recognition and limited diagnostic accuracy of current tools contributing to high morbidity and mortality. Conventional clinical scores (SOFA/qSOFA), standard biomarkers (CRP, PCT), and blood cultures suffer from delayed responsiveness, insufficient specificity, or slow turnaround, underscoring the urgent need for more reliable early diagnostic strategies. Presepsin, a soluble CD14 subtype generated during pathogen recognition by innate immune cells, has emerged as a promising biomarker with potential to reflect infection status earlier and more specifically than traditional markers. This systematic review and meta-analysis quantitatively evaluated the diagnostic accuracy of presepsin across diverse populations. PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies published between 2015 and 2025. Forty-seven studies involving 7,087 participants were included. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC), and likelihood ratios (PLR/NLR) with 95% confidence intervals (CI) were calculated using random-effects models. Heterogeneity was assessed with I² statistics, meta-regression, and subgroup analyses. Study quality was evaluated using QUADAS-2. Presepsin demonstrated excellent overall diagnostic performance: pooled sensitivity 0.84 (95% CI: 0.81–0.88), specificity 0.86 (95% CI: 0.80–0.90), DOR 32.23 (95% CI: 20.11–51.66), and AUC 0.91 (95% CI: 0.88–0.93). Subgroup analyses confirmed robust performance across settings and populations, with particularly high accuracy in neonates (sensitivity 0.90, specificity 0.92, AUC 0.96), followed by children (sensitivity 0.84, specificity 0.81, AUC 0.88, NLR 0.20) and adults (sensitivity 0.81, specificity 0.82, AUC 0.87). Meta-regression identified year of publication, geographic region, specimen type, population, and diagnostic criteria as key contributors to heterogeneity, but sensitivity analyses confirmed result stability. No significant publication bias was observed (p = 0.33). In conclusion, presepsin is a valuable and highly promising biomarker for sepsis diagnosis, showing favorable diagnostic accuracy across populations, with strongest utility in neonates. Its application in pediatric and adult patients warrants further validation through large, prospective, multi-center studies.

Aims: To investigate the global epidemiological characteristics of lower respiratory infection (LRI) burden caused by Streptococcus pneumoniae (SP) from 1990 to 2021. Methods: Using data from the Global Burden of Disease (GBD) study 2021, we systematically analyzed Streptococcus pneumoniae-related (SP-related) LRI burden, focusing on mortality, disability-adjusted life years (DALYs), and temporal trends by age, gender, geographic region, and socio-demographic index (SDI) quintiles. Decomposition analysis assessed the influence of epidemiological shifts, population growth, and aging on age-standardized mortality rates (ASMRs), while an autoregressive integrated moving average (ARIMA) model projected future trends. Results: Between 1990 and 2021, the global SP-related LRI death number decreased from 1,028,083 (95% uncertainty interval (UI): 923,782–1,146,074) to 505,268 (95% UI: 454,335–552,539), and the ASMR dropped from 19.28 (95% UI: 17.32–21.49) to 6.40 (95% UI: 5.76–7.00) per 100,000. The age distribution consistently exhibited a clear two-tiered pattern, gradually shifting from being predominantly composed of young children to being dominated by older adults. Disparities were stark across SDI quintiles, low-SDI regions exhibited up to 100-times-higher under-five mortality than high-SDI regions. Geographic distribution showed the highest ASMRs in sub-Saharan Africa and the lowest in Canada, the United States, and Australia, with Mongolia and Finland showing the largest reductions in mortality. Epidemiological changes were the most significant factor in ASMR reduction. Conclusions: The SP-related LRI burden has decreased globally but remains a major health concern, especially in low-SDI regions. Targeted public health interventions, particularly for neonates and elderly adults, are essential to address persistent disparities and further reduce mortality.

Sepsis remains a leading cause of global mortality and is characterized by a dysregulated host immune response to infection. Early deaths often result from hyperinflammation and organ dysfunction, whereas late-stage mortality is increasingly attributed to sepsis-induced immunosuppression, leading to secondary infections and viral reactivation. Challenges persist in the identification and management of sepsis-induced immunosuppression, including the lack of standardized immune monitoring methods, the absence of reliable immune biomarkers to guide therapy, and the limited success of immunomodulatory therapies in clinical trials. This review comprehensively summarizes the pathophysiology of sepsis-induced immunosuppression, encompassing immune cell apoptosis and exhaustion, the expansion and activation of immunomodulatory cells, metabolic reprogramming, epigenetic alterations, and iatrogenic factors. We also discuss current diagnostic challenges and explore emerging immunomodulatory strategies, such as cytokine therapies, immune checkpoint inhibitors, and metabolic modulators, as potential approaches to restore immune function. Finally, we highlight the importance of immune phenotyping and individualized precision medicine in the future management of sepsis, and integrating multidisciplinary approaches from mechanistic research to targeted therapies holds promise for improving patient outcomes.

Background: Pediatric sepsis, a life-threatening condition, often progresses to septic shock. However, microbiological and clinical profiles between pediatric sepsis patients with and without septic shock remain underexplored. Methods: This retrospective cohort study included 1200 pediatric sepsis patients (Phoenix Sepsis Score ≥ 2) from the Children’s Hospital of Chongqing Medical University between June 2018 and June 2023. Pediatric sepsis patients with septic shock were diagnosed based on the Phoenix Cardiovascular Score being ≥1. Clinical data and pathogens were taken from the electronic medical records and analyzed. Univariate and multivariable logistic regressions were conducted to identify the risk factors for septic shock. Results: Septic shock patients had longer hospital stays (14.8 vs. 12.0 days, p = 0.003) and higher mortality (17.4% vs. 4.7%, p < 0.001) when compared to non-septic-shock patients. Among these two groups, the pathogen prevalence revealed that bacterial pathogens dominated (48.9%), followed by viruses (10.3%). Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus remained the predominant pathogens; Pseudomonas aeruginosa and Mycoplasma pneumoniae were also increased. Combination antibiotic therapy was most frequent in patients with viral and fungal sepsis (79% and 86.5%, respectively). Patients with fungal sepsis had significantly longer hospital stays than those with viral sepsis (20.74 vs. 12.97 days, p = 0.017). Multivariable analysis identified that elevated lactate (OR = 1.49, 95% CI = 1.29–1.75) and pulmonary infection (OR = 2.25, 95% CI = 1.35–3.73) were independent risk factors for septic shock. Conclusions: Children with septic shock had higher mortality and prolonged hospitalization, with distinct microbiological profiles when compared with patients in the non-septic-shock group. Elevated lactate and presence of pulmonary infection are independent risk factors for septic shock. Early recognition of high-risk patients and tailored antimicrobial strategies are critical for improving outcomes.